testis and penis cancer...
TRANSCRIPT
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Testis and penis cancer atGenitourynary Cancers Symposium 2018
Testis and penis cancers are a rare and very rare disease, respectively.Research advancements in these diseases do not run as they do in frequent tumours.Among the small amount of new pieces of information, we picked up those studies we believe may impact the common practice, specially focussing on the most critical crossroads.
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Testis and penis cancer at Genitourynary Cancers Symposium 2018
Among these:- New markers for the diagnosis and monitoring in GCT (miRNA)- New drugs which may impact favorably (balance
efficacy/tolerability) in advanced penis cancer
Then we focus on critical issues in penis and testis cancer management:- Indication to post-chemo RPLND and role of referral centres for
GCT of the testis- Role and best sequences in patients with nodal metastases from
penile cancer.
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Testis. New markers on the blocks?
Mi-RNA as predictors of relapse
22 Giugno 2018
Simona SecondinoU.O.C. OncologiaFondazione IRCCS Policlinico San [email protected]
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Mi-RNA: what’s their role?
From Lin He, Nature Reviews 2004
Pri-microRNA (pri-miRNA) are first processedinto 70 nucleotide pre-miRNA inside thenucleus. Pre-miRNA are transported to thecytoplasm, and are procecessed into mi-RNA.
Only one strand of the mi-RNA in assembledinto the RNA-induced silencing complex(RISC), which subsequently acts on its targetby translational repression on mRNAcleavage, depending at least in part, on thelevel of complementarity between the smallRNA and its target.
Translational repressionPost-trascriptional gene silencing
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Mi-RNA: what’s their role?
• Markers (alfaFP, BetaHCG, LDH) are expressed in <60% of cases;
• Mi-RNA of the clusters miR-371-3 and miR-302/367 were suggested as new serumbiomarkers, and were detected in embryonic stem cell in GCT tissue;
• They are absent in other malignancies;
• Sensitivity 92%; specificity 80%;
Dieckmann, Eur Urol 2017
Diagnostic properties
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Mi-RNA: what’s their role?
Dieckmann, Eur Urol 2017
CS1N=77
Prognostic properties
CS2
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R. Leao, ASCO GU 2018
Serum mi-RNAs are predictive markers for viable disease post-chemotherapy
Hypothesis
Patients & Methods
Cohort A
Cohort B
N=39
N=43
Pre
Ch
emo
ther
apy
Po
st C
hem
oth
erap
y
Pre
RP
LND
Po
st R
PLN
D
N=39
N=82
N=39
miR-371a-3p
miR-373-3p
miR-367-3p
Mi-RNAs as predictive markers for viable disease
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R. Leao, ASCO GU 2018
Mi-RNAs as predictive markers for viable disease
Results
AFP
Classical tumor markers do not predict post-chemotherapy residual masses histology
BetaHCG LDH
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R. Leao, ASCO GU 2018
Mi-RNAs as predictive markers for viable disease
Results
miR-371a-3p
Serum miRNA levels are higher in the presence of viable GCT post-chemotherapy
miR-373a-3p miR-367-3p
Cohort A n=82; A ★★★p=0.002; B ★p=0.032
N=39
Serum miRNA levels post CT might supporttreatment decision in patients with residualretroperitoneal masses <3 cm
miR-371a-3p cut off level 2.0 (Sensitivity 100%, Specificity 54%; NPV 100%, p=0.02)
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Conclusions & take home message
• Serum miRNA are associated with clinical stage, treatmentresponse;
• miR-371a-3p as a single serum marker, highly sensitive andspecific, predicts viable disease, and might support treatmentdecision;
• More studies are needed to confirm these findings;
• Multi-institutional prospective studies with standard miRNAquantification assays are needed to estabilish miRNAs asclinical biomarkers
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Simona SecondinoU.O.C. OncologiaFondazione IRCCS Policlinico San [email protected]
Penis. Light (or night) chemotherapy for locally advanced disease:
Vinflunine trial
22 Giugno 2018
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Systemic therapy in advanced disease
Reference Regimen N° patients ORR Design
Hussein, 1990 Cisplatin-5FU 6 83% Retrospective
Shammas, 1992 Cisplatin-5FU 8 25% Retrospective
Pizzocaro, 1988 VBM (vincristina) 16 56% Retrospective
Haas (SWOG), 1999 PMB 40 32% Prospective
Pagliaro, 2010 TIP 30 50% Prospective
Theodore (EORTC),2008
Cisplatin-Irinotecan
26 31% Prospective
Nicholson, 2013 TPF 29 38.5% Prospective
Nicolai, 2016 TPF 47 43% Retrospective
Necchi, 2017 Dacomitinib 37 28% Prospective
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Study Design
Penile carcinoma: Vinflunine
Multicentre, single arm, phase II trial
TRIAL CRITERIA:
SCC
Locally advanced disease
▪ N2-N3
▪ T4
M1
ECOG (PS0-2)
Misurable disease
No prior CT/RT
TREATMENT
Vinflunine 320 mg/mq, q21 for 4 cycles
Patients with SD, RP, CR can continue until PD, or toxicities
ENDPOINTS
Primary endpoint
• Clinical benefit
Secondary endpoints
• ORR, PFS, OS, toxicity
Pickering, ASCO GU 2018
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Trial population
Penile carcinoma: Vinflunine
25 enrolled patients
22 evaluable patients
17 measurable patients
5 progressed prior to 4 cycles
7/22 patients with clinical benefit
Primary Endpoint7/22 patients, 45.5% (ORR+SD)
90% CI= 27.1-64.7; 95% CI = 24.4-67.8
Study has met primary endpoint
Secondary Endpoints
6/22 patients, 27.3% (ORR)
95% CI= 10.7-50.2
Pickering, ASCO GU 2018
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Secondary Endpoints
Penile carcinoma: Vinflunine
Pickering, ASCO GU 2018
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Systemic therapy in advanced disease
Reference Regimen N° patients ORR Design
Hussein, 1990 Cisplatin-5FU 6 83% Retrospective
Shammas, 1992 Cisplatin-5FU 8 25% Retrospective
Pizzocaro, 1988 VBM (vincristine) 16 56% Retrospective
Haas (SWOG), 1999 PMB 40 32% Prospective
Pagliaro, 2010 TIP 30 50% Prospective
Theodore (EORTC),2008
Cisplatin-Irinotecan
26 31% Prospective
Nicholson, 2013 TPF 29 38.5% Prospective
Nicolai, 2016 TPF 47 43% Retrospective
Necchi, 2017 Dacomitinib 37 28% Prospective
Pickering, 2018 Vinflunine 22 27% Prospective
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Conclusions & take home message
• The phase II or retrospective nature of the studies, and theirsmall sample size, and the lack of any randomized clinical trial,preclude assessment of a superior drug regimen in patientswith advanced disease;
• Multimodal management that combines systemic therapy withradical surgery yields modest survival rates, in advanceddisease;
• More studies are needed to identify also molecular markerswhich could lead to advances in new therapeutic strategies,coupled with renewed collaboration initiatives among high-volume centers
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Approccio MD e ruolo dei centri di riferimento nei tumori del testicolo
Giovanni Rosti, Simona Secondino
Oncologia, Policlinico San Matteo, IRCCS Pavia
Roma, 22 giugno 2018
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Vi sono ancora pazienti che ricevono un trattamento
subottimale o inadeguato o eccessivo (20-35%)*
* Heidenreich EAU 2017, Feldman ASCO 2018
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Cosa è richiesto
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Ma tutti sappiamo fare il PEB !
Verissimo, ma abbiamo una varietà notevole di PEB
per numero e per tipologia
Che fare con i fattori di crescita?
Che fare con anti-emesi?
Che fare con il riciclo di bleomicina?
Come pensare ai prossimi 40 anni del ragazzo?
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Esempio stadio 1 clinico
Radioterapia ? Sorveglianza ? Chemioterapia? Chirurgia?
Nessuna scelta è sbagliata.
Ognuna di queste scelta puo’ essere “sbagliata” in quella persona
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Che cosa offre un centro di riferimento ?
Multi-expertise in malattia rara
Accesso a studi clinici e nuovi farmaci
Terapie particolari (es. Alte Dosi e autotrapianto)
Situazioni cliniche particolari : sindrome OBS
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Months
Pro
babi
lity
0 6 12 18 24 30 36 42 48 54 60
0.0
0.2
0.4
0.6
0.8
1.0
42 42 32 29 26 26 24 24 23 23 23 HDCT43 41 37 31 29 28 27 27 27 26 25 PEB
Overall Survival, according to Treatment Arm
No. patients at risk
HDCT
PEB
P=0.6863
L’esperienza globale di un HV team
Necchi A, Ann Oncol 2015
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Beh! Come si spiega !!!
Tutti insieme appassionatamente
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«Advanced testis cancer patients of intermediate or poor prognosis
and relapsing patients should be managed in tertiary centers only.»
Heidenreich , EAU 2017
Siamo d’accordo? Un po’ sì e un po’ no
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Un ragazzo ha una malattia non seminomatosa
con metastasi polmonari e retroperitoneali
Alfa-feto da 2050 a 10 in 4 cicli
Resta malattia polmonare piccola (1cm) e RP piccola (2 cm)
Faccio altri due PE.
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Punti critici piu’ frequenti
Timing dei marcatori
Imaging adeguate
Sperm banking
Piccoli linfonodi e sedi «anomale»
Grandi produttori di beta HCG
Fretta nel trattare in seconda linea
Beh! Residuo piccolino lasciamo stare
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Ma dappertutto è uguale?
Alcune parti di Europa sopravvivenza circa 90%
Alcune parti Europa Centro-Orientale < 80%
In alcuni paesi stadi iniziali in minore numero
Estonia non seminoma met. sopravvivenza 47% Italia del Nord 85%
Ipotesi che in certe zone il trattamento sia peggiore
Nicolai N et al EJSO, in press 2018
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Paesi Bassi : miglioramento ultimi due decenni se PEB è PEB
allora la chirurgia ottimale fa la differenza (HV centers)
Bulgaria 75% dei pazienti trattati in 19 ospedali con MAV 12
Paesi Bassi 42 centri con MAV di 18 Belgio 40 centri MAV 8
Come mai?
Line Guida Nazionali e network nazionale
Nicolai N et al EJSO, in press 2018
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Allora i 2500 casi /anno in Italia devono tutti andare in questi
2 o 3 posti dove sono bravi?
NO
Accesso al centro di riferimento solo per situazioni particolari
Es. Chirurgia del residuo particolare, multistep ecc.
E se usassimo e-health technology?
Il MDT deve essere inteso anche come valutazione a distanza
per poi scegliere chi inviare.
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Divulgazione dell’approccio diagnostico
e terapeutico ai tumori del testicolo.
Che altro si puo’ fare?
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Probabilmente dopo ottenuta la remissione completa da due anni
non esistono piu’ il buono il brutto ed il cattivo, ma solo il “guarito”.
Follow-up Aspetto psicologico The care of the cured ones
+ tutto il resto
Dotarsi un goniometro a 361 gradi
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Post-chemotherapyRPLND
Current concepts
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Carver BS et al, J Clin Oncol 2007 Dec 10;25(35):5603-8.
Year of surgery
1989-1997 (n 291) 1998-2002 (n 213)
RP histology No of pts % No of pts % P value
Fibrosis 148 51 100 47 .8
Teratoma 98 34 101 47 .012
Teratoma with MalignantTransformation
7 3 7 3
Teratoma ± viable ca 120 41 106 50 .047
Viable ca 45 15 12 6 .001
Histology of the residual mass:proportion of viable cancer is about 10%
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Oechsle K et al. J Clin Oncol. 2008 Dec 20;26(36):5930-5
FDG-PET in metastatic NSGCT
NO ROLE OF FDG-PET IN NON-SEMINOMA
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There is unanymous consensus in candidating patients with an appreciable RM (≥ 1 cm) to RPLND
There is consensus in not candidating patients with complete remission to RPLND
The (first) dilemma is distinguishing patients with CR from those with a small RM!
The special case of the RM < 1 cm in NSGCT following first-line ChT
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# 558Fibrosis 71% (IQR 67-75)Teratoma 24% (IQR 20-27)Cancer 4% (IQR 1-7)
# 455 Overall recurrence: 5% (IQR 0-10)RP recurrence: 3% (IQR 0-5)FU from 4 to 15 years
Ravi P et al Annals of Oncology 25: 331–338, 2014
The special case of the RM < 1 cm in NSGCT following first-line ChTComparison between medical and surgical series
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The special cases for PC RPLND
• Residuals from seminoma
• Following salvage chemo
• Salvage surgery
• Late relapses and prognosis
• Mini-invasive PC-RPLND
• Maximal surgery
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The case of seminomatous RM
A PC RM in case of SGCT is very frequent (up to 80%)
Rate of vital disease rarely exceeds 10%
RM shape is irregular, very frequenly
Surgery is very difficult due to fibrotic scars and the complication rate is high
So far, the recomendation to surgery is very limited to veryselected cases
Peterson et al BJUI 2009;104:176-8
• Nodular RM (usually of ≥ 3 cm) suspicious to contain viable disease(or teratoma!)
• RM of seminoma displaying initial AFP elevation (15/40 or 37.5% withviable cancer, 12/40 or 30% with teratoma)
Debateble indication
Strong indication
Mosharafa AA, et al, J Urol 2003;169(6):2126-8
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Beck SDW et al J Clin Oncol 2005;23:6149-6156
Surgery performed in case of non-responsive disease (e.g. raised markers).
# 114 pts with elevatedtumor markers at PC-RPLND
50 1st line64 salvage
Period: 1977-20005-year OS: 53.9%61 (53.5%) alive ata medium FU of 72 mos
Salvage RPLND
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Issues in L-PC-RPLND
• L-PC-RPLND may represent a standard ifIt shows to be applicable in a significant (and probably increasing)
proportion of patients with a residual mass (not a sequence of special performances)
It demonstrates a better tolerability profile than open PC-RPLND
Oncologic results are comparable with those of open PC-RPLND
Nicolai N et Al, J Endourol 2016, in press
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Available data in MI-RPLND
issue Lap-RPLND RA-RPLND Comments
No of pts 323 57 Significant difference
Stage II B 183 na Small to medium size residual masses in both techniques
Median size peCht 21-27 mm na
Median size pre RPLND 3-60 mm 12-70
Histology FN/T/Ca 157/137/21 34/22/1 Usually favourable histology
FU 1-222 mos 1-58 mos Short to medium for Lap, very short for RA
recurrences 8 0 or na Few recurrences
OT 116-700 min 129-527 min Similar OT
Major complications 13 na Few complicaions in Lap
LAE 3.4% na Very low rate in Lap
HS 2-5 2-4 Similar duration
Albqami 2005, Maldonado 2007, Permpongkosol 2009, Aufderklamm 2009, Steiner 2013, Nicolai 2016
Annerstedt 2008, Kamel 2012, Cost2012, Cheney 2014, Harris 2015, Stepanian 2017, Singh 2017, Doumerc 2018
Lap-RPLND RA-RPLND
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The concept of maximal surgery
• An AP is required in about 20 to 30% of patients
• Risk Factors for AP: RM size(> 5 cm), histology (viablecancer) and raised markers
• An AP associated with longerhospital stay and complications
• The most frequent APs:• Nephrectomy• Hepatic resections• Vascular resections
• Heidenreich A et al, Eur Urol 2009;55:217-226
• Cary C et al, Urol Oncol: Semin Origin Invest, 2015; in press
Additional procedures (AP)
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Fizazi K et al. Ann Oncol 19: 259–264, 2008
Viable Cancer proportion (%)Risk Category (IGCCC)Radicality
Maximal Surgery
Most of the APs can be foreseen (but some not!)
An expert surgeons team is needed
Prognostic factors in case of viable cancer
Heidenreich A et al, Eur Urol 2009;55:217-226
Cary C et al, Urol Oncol: Semin Origin Invest, 2015;33(9):389
The concept of maximal surgery (2)
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Standard RPLND
Maximal RPLND with aorta and IVC replacementfollowing salvage therapy
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Penile carcinoma. The best sequence for nodal metastases
Current concepts
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Management of regional lymph nodes: guidelines
EAU Guidelines Penile Cancer, 2016
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Palpable inguinal nodes (cN1-cN2-cN3)
EAU Guidelines Penile Cancer, 2016
H Van Poppel, Ann Oncol 2013
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Palpable inguinal nodes (cN1-cN2)
H Van Poppel, Ann Oncol 2013T Machado, J Urol 2007
RISK factors for pelvic N+
ILN≥3
Extranodal
extension
Diameter
30mm
57,1%
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Adjuvant chemotherapy in N+
H Van Poppel, Ann Oncol 2013
Adjuvant
chemotherapy
RR 30% (cisplatin, bleomycin and methotrexate)Leijte, Eur Urol 2007
Hakenberg, BJU Int 2006
RR 38-50% (T-PF or TIP)Nicholson, Br J Cancer 2013
Nicolai, Clinic Genit Cancer 2016
Which drugs?
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Adjuvant chemotherapy in N+
Adjuvant
chemotherapy
Only Surgery(Pandey 2006)
Adj CT(Noronha 2012)
Inguinal N+ 53.1% 66%
Pelvic N+ 28.6% 46%
Two-year overall survival
Pandey, J Surg Oncol 2006Noronha, Urol Annals 2012
OS according to number of cycles
N=19
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Neo-Adjuvant chemotherapy in N+
Pagliaro, JCO 2010
Neo-Adjuvant
chemotherapy
PFS 8.1 mo
OS 17 mo
N=30
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Neo-Adjuvant chemotherapy in N+
EAU Guidelines Penile Cancer 2016
Neo-Adjuvant
chemotherapy
N RR pCR
Leijite2007
20 63% 10%
Pagliaro 2010
30 50% 13%
Nicolai2016
28 43% 14%
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EAU vs NCCN guidelines
EAU Guidelines Penile Cancer 2016
Neo-Adjuvant
chemotherapy
cN3
Adjuvant
chemotherapy
NCCN Guidelines Penile Cancer 2016
>4 cm
“There are no sufficient data to form conclusionsabout the use of adjuvant treatment”
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Adjuvant vs Neoadjuvant chemotherapy
Nicolai N, Eur J Urol 2016
P=0.15 P=0.25
N=47 N=47
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Clinical casesSIU-UPDATE June 22th, 2018
Testis tumour context
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Clinical presentation
Nov 2016
26 yrs old
Left testicular firm nodule (20 mm)
US: hypoechoic lesion on lower testis pole
STM: AFP 14 ng/ml
January 12 th, 2017 Elevated markers: AFP 242 ng/ml, beta-hCG 367
Left orchidectomy
Definitive pathology: postpubertal teratoma
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Clinical presentationMarch 2017
AFP and beta-hCG reduced and then increased (AFP 390; beta-hCG420; LDH N
whole body CT scans
Two small paraortic enlarged lymph-nodes One small left supraclavicular lymph-node
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Staging
• Stage pT1, cN2 M0 S1 (good risk)
• Stage II B positive markers
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Which therapy?
• Observation: check again until nodes are clearly largerthan 3 cm
• First line chemotherapy• 3 courses of PEB• 4 courses of PEB
• Primary RPLND• Open bilateral• Miniinvasive unilateral
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Which therapy?
• Observation: check again until nodes are clearly largerthan 3 cm
• First line chemotherapy• 3 courses of PEB• 4 courses of PEB
• Primary RPLND• Open bilateral• Miniinvasive unilateral
2018 EAU guidelines; 2018 NCCN guidelines
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Actual therapy
• March 2017 → May 2017: 3 courses of PEB (BLM 9/9)
• Markers normalised after 2 nd course
• Chest and abdominal CT scans
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CT scans on July 18 th, 2017
Nodes enlarged of some mm
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What happened?
• Mixed response
• No response
• Progressive disease
• Complete biological response with a residualgrowing mass
• I do not know
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What to do?
• Continue with another 1-3 courses of PEB
• Salvage Chemotherapy (VIP/TIP/High Dose)
• Surgery (RPLND and neck LND)
• Radiation therapy
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Surgery
• 10.2017 Mini-invasive (laparoscopic) unilateralRPLND: postpubertal teratoma in 4/18 paraorticand iliac lymph-nodes
• Antegrade ejaculation maintained
• 1.2018 Neck LAD: postpuertal teratoma in 1/20 lymph-nodes
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2nd case (from 2018 GU Symposium)
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Clinical cases context and debate. Role of expert and referral centers for post-chemo surgery: when, which and
where
Caso clinico 3A.E. 1984
12.2013 Riscontro occasionale nodulo testicolare destro27.01.2014 TAC: linfonodo interaortocavale sottorenale 30x30mm02.2014 LDH 357, AFP 69, betaHCG 488
10.02.2014 orchifunicolectomia destra con protesi.E.I.:Il didimo è quasi completamente occupato dauna neoplasia di 5,5 cm di asse maggiore, biancastra, emorragica e necrotica, limitata al didimo.Diagnosi istopatologica:Carcinoma embrionario estesamente necrotico-emorragico con prevalente pattern di crescita di tipo tubulo-ghiandolare e papillare. Rete testis ed epididimo esenti da neoplasia. Assenza di invasione vascolare.Staging: pT1 pNx
MDM: consigliata CT
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10.03.2014 betaHCG 1298
Dal 10.03.2014 al 23.05.2014 4 cicli di PEB
23.05.2014 Markers neg
10,07,2014 TAC: linfonodo retroperitoneale ridotto a 23x16mm
MDM
05,08,2014 open RPLND: E.I. focolai teratoma cistico
Da allora FU neg
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Caso clinico 4D.M. 1990
08.2017 Riscontro occasionale aumento testicolare sinistro05.10.2017 TAC: linfoadenopatia lomboaortica 3.6cm sottorenale19.10.2017 LDH 280, AFP 92, betaHCG 3,3
24.10.2017 orchifunicolectomia sinistra con protesi.E.I.: Testicolo di 5,3x3,5x3 cm con una neoplasia di 3,9 cm di asse maggiore, in parte solida ed in parte microcistica, focalmente emorragica, limitata al parenchima testicolare.Diagnosi istopatologica:A) Tumore a cellule germinali misto limitato al testicolo, con prevalente componente di carcinoma embionario (75%) associata a ridotta componente di teratoma postpuberale (20%) con focolaio di atipia (c.d.: teratoma immaturo) ed a focale tumore del sacco vitellino (5%) associati a neoplasia germinale in situ, necrosi e di focale diffusione pagetoide alla rete testis. Tonaca albuginea esente da neoplasia. Assenza di invasione vascolareStaging: pT1 pNx
MDM: consigliata CT
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28.11.2017 AFP 185, betaHCG 1,2
Dal 28.11.2017 al 14.01.2018 3 cicli di PEB
19.02.2018 Markers neg
26.02.2018 TAC: linfoadenopatia paraortica sinistra di 30mm di asse corto
MDM
05.08.2014 RA- RPLND:E.I.: A)Nodulo solido-cistico di 4,8 cm ed un frammento di tessuto adiposo di 7 cm da cui si isolano B) dodici linfonodi antero e para-aortici.Diagnosi istopatologica:A) Metastasi di tumore delle cellule germinali del testicolo in forma di teratoma.Istiocitosi dei seni nei linfonodi esaminati
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Clinical casesSIU-UPDATE June 22th, 2018
Penis tumour context
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• 66 yrs old
• Glans lesion treated with corticosteroid for three months
• Rapid growth in one month
• Appearance of bilateral groin masses
• Comorbidities: smoker (20 per day), mild diabetes, mild hypertension
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What to do?
• Primary chemotherapy
• Clinical trial
• Chemotherapy followed by RT
• Primary surgery• Amputation and groin dissections
• Amputation, groin and pelvic disection
• Emasculation and inguinopelvic dissection
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What to do?
• Primary chemotherapy
• Clinical trial
• Chemotherapy followed by RT
• Primary surgery• Amputation and groin dissections
• Amputation, groin and pelvic disection
• Emasculation and inguinopelvic dissection
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En-bloc excision of primary tumour (total amputation), Bilateral orcheictomy, skin and left groin mass
Completion of inguinal LND
Final aspect ofbilateral ILND and emasculation
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Pelvic LND
Pelvic LND
Final aspect ofpelvic LND
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End of intervention and closure
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Which is the best sequence for nodal
metastases from penile carcinoma?
CASE 2
PENILE SCC WITH SINGLE PALPABLE NODE
(cN1)
Staging
Inguinal ultrasound: positive node on the right side.
Chest + abdomen CT: negative.
Management
✓ Glansectomy
✓ Bilateral inguinal lymph node dissection.
Pathology
Squamocellular carcinoma, involving the corpus
spongiosum (max depth 6 mm) with peritumoral
vascular invasion. Free surgical margins.
Node metastasis in 1/15 nodes (right side)
Staging: pT2 pN1
Grading: G2
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Which is the best sequence for nodal
metastases from penile carcinoma?
CASE 3 - PENILE SCC WITH FIXED NODES (cN3)
Physical examination
✓ Necrotic lesion involving the glans penis.
✓ Large, fixed, palpable nodes involving both inguinal
regions.
Staging
✓ Inguinal ultrasound: bilateral enlarged nodes.
✓ Chest + abdomen CT
chest: negative;
gross bilateral inguinal adenopathies.
✓ PET/CT scan
positive inguinal nodes bilaterally;
no pelvic positivities.
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Which is the best sequence for nodal
metastases from penile carcinoma?
CASE 3 - PENILE SCC WITH FIXED NODES (cN3)
Management – Step 1
Neoadjuvant chemotherapy with paclitaxel, ifosfamide and cisplatin.
→ Objective and radiologic response.
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Which is the best sequence for nodal
metastases from penile carcinoma?
CASE 3
PENILE SCC WITH FIXED NODES (cN3)
Management – Step 2
✓ Glansectomy
→ intraoperative positive margins
→ radical penectomy with perineal
urethrostomy
Squamocellular carcinoma involving the distal
urethra and both corpora cavernosa.
pT3 G3
✓ Radical bilateral inguinal lymphadenectomy
3/11 positive nodes on the right side
2/15 positive nodes on the left side
pN2
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Which is the best sequence for nodal
metastases from penile carcinoma?
CASE 3
PENILE SCC WITH FIXED NODES (cN3)
Management – Step 3
Bilateral pelvic lymph node dissection
→ 25 negative nodes
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Conclusions
mi-RNAs may represent a new device for staging and FU of markers negative GCT of the testis (80% of S and 40% of NS)
Post-chemo RPLND should be performed in referral centres.RPLND is not usually indicated in seminomaMI-RPLND is admitted in selected situations.Maximal surgery must be planned prior to surgery with multidisciplinary surgical team.
Systemic chemotherapy (CHT) has a moderate efficacy and displays a relevant toxicity. ‘New’ drugs (Vinflunine) are awaited in this setting.
Neo-adjuvant CHT is active in inducing responses and adjuvant CHT maintains complete remissions in some N+ case. Surgery remains the milestone of treatment in N+ patients and neo-adjuvant or adjuvant chemotherapy should be considered according to resectability and following final histology.
Testis Cancer Penile Cancer
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Thanks to
Panelists
Prof. Ottavio De Cobelli, IEO MilanoDott. Giovanni Rosti, Policlinico San Matteo PaviaDott. Simona Secondino, Policlinico San Matteo Pavia
Raffaella LonghiFederica BaldrighiAndrea Canton
Società Italiana di Urologia
Dott. Nicola Nicolai, INT Milano